Effect of active immunization with IL-17A on B cell
function and infection risk in pristane-induced lupus
Mirza Zaka PRATAMA,
Dita Kartika SARI,
Haﬁshtyawan Maulidyananta AGDANA,
Keryasta Becik KAWUNINGAN,
and Handono KALIM
Department of Clinical Pathology,
Rheumatology and Immunology Division, Department of Internal Medicine, and
Degrees of Biomedical Sciences, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
Purpose: The aim of this study was to determine the effect of active immunization of interleukin (IL)-17A to
inhibit B cell functions and monitor the risk of infection in a pristane-induced lupus mice model.
Methods: Female Balb/c mice were given a single intraperitoneal injection of 0.5 mL pristane. IL-17A was cou-
pled to keyhole limpet hemocyanin (KLH) and given to mice in three different doses: D0 (0 lg/mL), D1 (1 lg/
mL), and D2 (10 lg/mL). The vaccine was given three times with 3-week intervals. At day 42, mice were injected
intraperitoneally with methicillin-resistant Staphylococcus aureus (MRSA) and monitored for 3 weeks. Plasma
cells proliferation, Th17 and plasma cell percentages were measured by ﬂow cytometry; anti-IL-17A antibody
titers, IL-17A, and anti-double-stranded DNA (anti-dsDNA) levels were measured by enzyme-linked
immunosorbent assay; and MRSA colonization was measured by bacterial counter.
Results: Anti-IL-17A antibody titers were signiﬁcantly higher in D2 compared to D0 (P = 0.012). Serum IL-17A
levels were also signiﬁcantly lower in D2 compared to D0 (P = 0.000) while Th17 percentages were not signiﬁ-
cantly different between groups. D2 was also had signiﬁcantly lower anti-dsDNA (P = 0.021), lower plasma cell
percentages (P = 0.000) and lower B cell proliferation rate (P = 0.001) compared to D0. Analysis for the risk of
infection also revealed that D2 did not increase the risk of infection compared to D0 (P = 0.504).
Conclusion: Active immunization with IL-17A coupled to KLH was able to induce a high titer of neutralizing
antibodies against IL-17A and inhibit B cell functions without increasing the risk of infection in a pristane-
induced lupus mice model.
Key words: interleukin-17A, kinoid vaccine, systemic lupus erythematosus.
The pathogenesis of systemic lupus erythematosus
(SLE) consists of several interactions in the immune sys-
For some time, autoantibody production and
deposition of the immune complex have been believed
to be the hallmark features of SLE.
However, there is
growing evidence that several cytokines have patho-
genic roles in the disease.
One example of these
cytokines is interleukin (IL)-17.
IL-17 is a proinﬂammatory cytokine which has multi-
ple functions for the regulation in tissue inﬂammation.
IL-17 is mainly produced by Th17, one of the CD4+ T
Different subtypes of IL-17 exist but only
Correspondence: Dr Mirza Zaka Pratama, Rheumatology and
Immunology Division, Department of Internal Medicine, Fac-
ulty of Medicine, Universitas Brawijaya, Malang 65145,
Indonesia. Email: email@example.com
© 2018 Asia Paciﬁc League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd
International Journal of Rheumatic Diseases 2018; 21: 1277–1286